The IAI-OCTA Study; a Study of OCT-Angiography Analysis Efficacy

Sponsor
University of California, Los Angeles (Other)
Overall Status
Completed
CT.gov ID
NCT03022292
Collaborator
Regeneron Pharmaceuticals (Industry)
26
1
1
41.1
0.6

Study Details

Study Description

Brief Summary

A study investigating the ability of OCTA imaging technology to identify and analyze untreated type 1, 2, and 3 neovascular membrane lesions in treatment naive patients with exudative macular degeneration, as well as investigating the ability of the OCTA imaging technology to evaluate the treatment outcomes of Intravitreal Aflibercept Injection in neovascular lesions associated with macular degeneration.

This study is utilizing a new, FDA approved, non-standard of care technology (OCT-Angiography by Optovue) to image and evaluate the treatment outcomes of using standard of care Intravitreal Aflibercept Injections for their approved use in patients diagnosed with neovascular AMD who are naive to previous Anti-VEGF therapies.

Condition or Disease Intervention/Treatment Phase
  • Drug: Aflibercept Ophthalmic
  • Device: optovue angiovue
Phase 4

Detailed Description

Prospective study of neovascular AMD subjects with type 1, 2, or 3 neovascularization that have not been treated with prior anti-VEGF therapy. Subjects will be scheduled for intravitreal aflibercept injection (IAI) at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Additional injections can be administered during the remaining visits on an as needed basis per PI discretion based on the presence of any intraretinal or subretinal fluid on OCT, heme visualized on examination, reduction of BCVA by 5 or more ETDRS letters, or evidence of either increased area, density, or activity of the brush border of the neovascularization on OCT angiography. There will be a minimum of 21 days between subsequent injections. Each subject will therefore receive a minimum of 7 injections and up to a maximum of 13 injections throughout the study period. No injection will be given on the exit visit, week 52. OCT angiography and spectral domain OCT imaging will be performed at baseline and every 4 weeks thereafter

The above procedures are standard of care for neovascular AMD subjects.

As part of this study, these subjects will also undergo imaging of both eyes with OCTA at each visit. This is not standard of Care and is research.

The only procedure that is being performed for research is the OCT-A. The injections and all other procedure are SOC based on physician discretion and clinical need. The investigators will not be modifying the dosage amounts or frequency.

A subgroup of willing subjects will undergo OCT angiography every 2 weeks for the first 12 weeks.

Indocyanine green angiography will be performed at baseline for all subjects to establish baseline subject population characteristics. Fluorescein angiography will be performed at baseline, week 12, and week 52 for efficacy monitoring. Detailed OCT angiography analysis will be performed to identify anatomical and morphological biomarkers of growth progression and disease activity. In addition to qualitative structural and morphological analysis, detailed quantitative OCT angiography analysis of the neovascular lesion using automated or manual capillary density maps and area calculation will be performed at each visit to determine the detailed microvascular response of neovascular complexes to IAI therapy.

Study Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
The IAI-OCTA Study or; Microvascular Structure and Morphology of Neovascular Membranes in Age Related Macular Degeneration (AMD) After Intravitreal Aflibercept Injection (IAI) Therapy Using OCT-Angiography Analysis
Actual Study Start Date :
Mar 30, 2017
Actual Primary Completion Date :
Jun 25, 2020
Actual Study Completion Date :
Aug 31, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: IAI Treatment

Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Additional injections can be administered during the remaining visits on an as needed basis per Primary Investigator (PI) discretion based on the presence of any intraretinal or subretinal fluid on OCT, heme visualized on examination, reduction of BCVA by 5 or more ETDRS letters, or evidence of either increased area, density, or activity of the brush border of the neovascularization on OCT-angiography. There will be a minimum of 21 days between subsequent injections. Each subject will therefore receive a minimum of 7 injections and up to a maximum of 13 injections throughout the study period.

Drug: Aflibercept Ophthalmic
IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC

Device: optovue angiovue
FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
Other Names:
  • OCTA
  • Outcome Measures

    Primary Outcome Measures

    1. Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan. [Week 24]

      Area of the neovascular lesion (in millimeters^2)

    2. Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan. [Week 52]

      Area of the neovascular lesion (in millimeters^2)

    Secondary Outcome Measures

    1. Best Corrected Visual Acuity (BCVA) -Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Change [Baseline, Week 24]

      patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).

    2. Best Corrected Visual Acuity (BCVA) -ETDRS Letter Change [Week 24, Week 52]

      patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).

    3. Mean Best Corrected Visual Acuity (BCVA) [Week 24]

      Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.

    4. Mean Best Corrected Visual Acuity (BCVA) [Week 52]

      Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.

    Other Outcome Measures

    1. OCTA Neovascular Membrane Regression Ratio of Change [12 weeks]

      OCT angiography regression of neovascular membrane as measured by ratio of change in area of the neovascular lesion (in millimeters^2) during the initial 12 weeks

    2. Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan. [week 24]

      Participants with presence of intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)

    3. SD OCT Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM) [week 52]

      Participants with presence of SD OCT intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)

    4. Ocular AE [52 weeks]

      ocular adverse events

    5. Relevant Systemic SAE [52 weeks]

      relevant systemic serious adverse events

    6. Number of Injections [week 24]

    7. Number of Injections [week 52]

    8. OCTA Neovascular Membrane Biomarker Qualitative Analysis (Sub-study) [Week 1-12]

      In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including attenuation of the fringe during the initial 12 weeks

    9. SD OCT Analysis of Central Macular Thickness [Baseline to week 24]

      Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.

    10. SD OCT Analysis of Central Macular Thickness [Baseline to week 52]

      Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.

    11. OCTA Analysis of Vessel Density [24 weeks]

      OCT angiography ratio of change in neovascular membrane as measured by area of the neovascular lesion in mm^2 at baseline and week 24. Ratio of change was calculated as change from baseline divided by the baseline value.

    12. OCTA Neovascular Membrane Biomarker Qualitative Analysis of Flow-void Areas(Sub-study) [Week 1-12]

      In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks) OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including presence of flow-void areas during the initial 12 weeks

    13. OCTA Neovascular Membrane Biomarker Qualitative Analysis of Vessel Looping (Sub-study) [Week 1-12]

      In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks) OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including changes in vessel looping during the initial 12 weeks

    14. SD OCT Analysis of SRF Volume [week 24 and 52]

      Change in volume of subretinal fluid

    15. SD OCT Analysis of SHRM Volume [week 24 and 52]

      Change volume of SHRM

    16. Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan. [week 24]

      Participants with presence of cystoid macular edema

    17. Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan. [week 52]

      Participants with presence of cystoid macular edema

    18. Pigment Epithelial Detachment (PED) Volume as Determined by SD OCT Analysis [Baseline to week 24]

      Change in ratio of volume of pigment epithelial detachment (PED), calculated as change from baseline divided by baseline value.

    19. PED Volume as Determined by SD OCT Analysis [Baseline to Week 52]

      Change in ratio of volume of PED, calculated as change from baseline divided by baseline value.

    20. PED Height as Determined by SD OCT Analysis [Baseline, week 24]

      Ratio of change in height of PED, calculated as change from baseline divided by baseline value

    21. PED Height as Determined by SD OCT Analysis [Baseline, week 52]

      Ratio of change in height of PED, calculated as change from baseline divided by baseline value

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Subject is older than 50 years of age.

    2. Subject is willing to participate in the study and able to follow the study criteria and protocol.

    3. The study eye is treatment naive regarding treatment of neovascular AMD.

    4. Subject is willing and able to comply with clinic visits and study-related procedures.

    5. Subject is able to provide signed informed consent.

    6. Subject is able to understand and complete study-related questionnaires.

    7. The subject is not currently involved with any other clinical study.

    8. Best Corrected Visual Acuity (BCVA) with ETDRS Snellen equivalent of 20/400 or better and 20/32 or worse.

    9. Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and fundus photography (FP).

    10. Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of ocular hypotensive agents.

    11. Prior focal corticosteroid treatment is allowed, as long as the study eye is not involved. However prior (within 90 days of Day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted.

    Exclusion Criteria:
    1. Any prior treatment of neovascular AMD in the eye proposed for enrollment including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior intravitreal treatment for neovascular AMD (except minerals and vitamins).

    2. Known serious allergies to aflibercept, fluorescein dye, Indocyanine Green (ICG), shellfish, drugs for pupillary dilation, topical anesthetic, or sterilizing solution (e.g. Betadine Solution).

    3. Prior or current systemic anti-VEGF therapy.

    4. Pregnant or breast-feeding women.

    5. Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly).

    6. Contraindication to pupillary dilation in study eye.

    7. Any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements.

    8. Presence of any advanced systemic condition or end-stage disease, such as advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study.

    9. Previous therapeutic radiation in the region of the study eye.

    10. Prior retinal pigment epithelial (RPE) tear in study eye.

    11. Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days.

    12. Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months.

    13. Prior vitrectomy in the study eye.

    14. Presence of any causes of CNV and PED other than due to AMD or presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stein Eye Institute of UCLA Los Angeles California United States 90095

    Sponsors and Collaborators

    • University of California, Los Angeles
    • Regeneron Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    David Sarraf, MD, Principal Investigator, University of California, Los Angeles
    ClinicalTrials.gov Identifier:
    NCT03022292
    Other Study ID Numbers:
    • 16-000925
    First Posted:
    Jan 16, 2017
    Last Update Posted:
    Jan 6, 2022
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Period Title: Overall Study
    STARTED 26
    COMPLETED 24
    NOT COMPLETED 2

    Baseline Characteristics

    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Overall Participants 26
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    23
    88.5%
    >=65 years
    3
    11.5%
    Sex: Female, Male (Count of Participants)
    Female
    6
    23.1%
    Male
    20
    76.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    11.5%
    Not Hispanic or Latino
    22
    84.6%
    Unknown or Not Reported
    1
    3.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    3.8%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    2
    7.7%
    White
    19
    73.1%
    More than one race
    0
    0%
    Unknown or Not Reported
    4
    15.4%
    Region of Enrollment (participants) [Number]
    United States
    26
    100%
    Mean BCVA in LogMAR (score) [Mean (Full Range) ]
    Mean (Full Range) [score]
    0.32
    OCTA Analysis of Lesion Area (mm^2) [Mean (Full Range) ]
    Mean (Full Range) [mm^2]
    2.008

    Outcome Measures

    1. Primary Outcome
    Title Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
    Description Area of the neovascular lesion (in millimeters^2)
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants present for 24 week assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Full Range) [mm^2]
    1.07
    2. Primary Outcome
    Title Area of Lesion Measured by Optical Coherence Tomography Angiography (OCTA) Scan.
    Description Area of the neovascular lesion (in millimeters^2)
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants present for 52 week assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 20
    Mean (Full Range) [mm^2]
    0.67
    3. Secondary Outcome
    Title Best Corrected Visual Acuity (BCVA) -Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Change
    Description patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).
    Time Frame Baseline, Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants with analyzable ETDRS at both baseline & week 24
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 23
    ≥5 ETDRS letters
    4
    15.4%
    ≥10 ETDRS letters
    2
    7.7%
    ≥15 ETDRS letters
    0
    0%
    4. Secondary Outcome
    Title Best Corrected Visual Acuity (BCVA) -ETDRS Letter Change
    Description patients with gain of ≥5, ≥10, or ≥15 ETDRS letters. The ETDRS chart is read at 4.0 meters, and presents a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows, for a total of 14 lines (70 letters).
    Time Frame Week 24, Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants with analyzable BCVA at both 24 and 52 weeks
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 21
    ≥5 ETDRS letters
    4
    15.4%
    ≥10 ETDRS letters
    1
    3.8%
    ≥15 ETDRS letters
    0
    0%
    5. Secondary Outcome
    Title Mean Best Corrected Visual Acuity (BCVA)
    Description Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants with analyzable measure at week 24
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Full Range) [score]
    0.3
    6. Secondary Outcome
    Title Mean Best Corrected Visual Acuity (BCVA)
    Description Visual acuity (VA) was assessed at a distance of 4 meters from Snellen and converted to logarithm minimum angle of resolution (logMAR). A logMAR value of 0 equates to 20/20 Snellen visual acuity (normal distance eyesight), with a lower logMAR value indicating better visual acuity.
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants with analyzable BCVA at 52 weeks
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 22
    Mean (Full Range) [score]
    0.33
    7. Other Pre-specified Outcome
    Title OCTA Neovascular Membrane Regression Ratio of Change
    Description OCT angiography regression of neovascular membrane as measured by ratio of change in area of the neovascular lesion (in millimeters^2) during the initial 12 weeks
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 26
    Mean (Inter-Quartile Range) [ratio]
    0.37
    8. Other Pre-specified Outcome
    Title Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
    Description Participants with presence of intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)
    Time Frame week 24

    Outcome Measure Data

    Analysis Population Description
    Participants present for assessment at week 24
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    intraretinal
    4
    15.4%
    subretinal
    9
    34.6%
    SHRM
    1
    3.8%
    9. Other Pre-specified Outcome
    Title SD OCT Presence of Intraretinal and Subretinal Fluid, and Subretinal Hyper-Reflective Material (SHRM)
    Description Participants with presence of SD OCT intraretinal and subretinal fluid, and Subretinal Hyper-Reflective Material (SHRM)
    Time Frame week 52

    Outcome Measure Data

    Analysis Population Description
    Participants present for assessment at 52 weeks
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 22
    intraretinal
    3
    11.5%
    subretinal
    6
    23.1%
    SHRM
    0
    0%
    10. Other Pre-specified Outcome
    Title Ocular AE
    Description ocular adverse events
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants at risk for AE
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 26
    Number [events]
    2
    11. Other Pre-specified Outcome
    Title Relevant Systemic SAE
    Description relevant systemic serious adverse events
    Time Frame 52 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants at risk for AE during study
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 26
    Number [events]
    1
    12. Other Pre-specified Outcome
    Title Number of Injections
    Description
    Time Frame week 24

    Outcome Measure Data

    Analysis Population Description
    Participants present at week 24 visit
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 25
    Number [injections]
    25
    13. Other Pre-specified Outcome
    Title Number of Injections
    Description
    Time Frame week 52

    Outcome Measure Data

    Analysis Population Description
    Participants present for week 52 visit
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 22
    Number [injections]
    12
    14. Other Pre-specified Outcome
    Title OCTA Neovascular Membrane Biomarker Qualitative Analysis (Sub-study)
    Description In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including attenuation of the fringe during the initial 12 weeks
    Time Frame Week 1-12

    Outcome Measure Data

    Analysis Population Description
    Qualitative analyses not performed due to study staff turnover and lack of expertise
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 0
    15. Other Pre-specified Outcome
    Title SD OCT Analysis of Central Macular Thickness
    Description Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    Participants present for both baseline and week 24 assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Standard Deviation) [ratio]
    0.08
    (0.27)
    16. Other Pre-specified Outcome
    Title SD OCT Analysis of Central Macular Thickness
    Description Ratio of change in SD OCT central macular thickness, calculated as change between visits divided by baseline measure.
    Time Frame Baseline to week 52

    Outcome Measure Data

    Analysis Population Description
    Participants present for both baseline and week 52 assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Standard Deviation) [ratio]
    0.07
    (0.25)
    17. Other Pre-specified Outcome
    Title OCTA Analysis of Vessel Density
    Description OCT angiography ratio of change in neovascular membrane as measured by area of the neovascular lesion in mm^2 at baseline and week 24. Ratio of change was calculated as change from baseline divided by the baseline value.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants present for both baseline and 24 week assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Standard Deviation) [ratio]
    -0.12
    (2.73)
    18. Other Pre-specified Outcome
    Title OCTA Neovascular Membrane Biomarker Qualitative Analysis of Flow-void Areas(Sub-study)
    Description In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks) OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including presence of flow-void areas during the initial 12 weeks
    Time Frame Week 1-12

    Outcome Measure Data

    Analysis Population Description
    Qualitative analyses not performed due to study staff turnover and lack of expertise
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 0
    19. Other Pre-specified Outcome
    Title OCTA Neovascular Membrane Biomarker Qualitative Analysis of Vessel Looping (Sub-study)
    Description In subjects participating in the sub-study of serial OCT Angiography during the initial 12 weeks) OCT angiography qualitative analysis of morphological biomarkers of the neovascular complex including changes in vessel looping during the initial 12 weeks
    Time Frame Week 1-12

    Outcome Measure Data

    Analysis Population Description
    Qualitative analyses not performed due to study staff turnover and lack of expertise
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 0
    20. Other Pre-specified Outcome
    Title SD OCT Analysis of SRF Volume
    Description Change in volume of subretinal fluid
    Time Frame week 24 and 52

    Outcome Measure Data

    Analysis Population Description
    Fluid volume measures not performed due to study staff turnover and lack of expertise
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 0
    21. Other Pre-specified Outcome
    Title SD OCT Analysis of SHRM Volume
    Description Change volume of SHRM
    Time Frame week 24 and 52

    Outcome Measure Data

    Analysis Population Description
    Fluid volume measures not performed due to study staff turnover and lack of expertise
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 0
    22. Other Pre-specified Outcome
    Title Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
    Description Participants with presence of cystoid macular edema
    Time Frame week 24

    Outcome Measure Data

    Analysis Population Description
    Participants assessed for CME at week 24
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 23
    Count of Participants [Participants]
    4
    15.4%
    23. Other Pre-specified Outcome
    Title Presence of CME (Cystoid Macular Edema) on Spectral Domain Optical Coherence Tomography (SD-OCT) Scan.
    Description Participants with presence of cystoid macular edema
    Time Frame week 52

    Outcome Measure Data

    Analysis Population Description
    Participants assessed for CME at week 52
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 23
    Count of Participants [Participants]
    3
    11.5%
    24. Other Pre-specified Outcome
    Title Pigment Epithelial Detachment (PED) Volume as Determined by SD OCT Analysis
    Description Change in ratio of volume of pigment epithelial detachment (PED), calculated as change from baseline divided by baseline value.
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    Participants present for both baseline and week 24 assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Standard Deviation) [ratio]
    0.18
    (0.6)
    25. Other Pre-specified Outcome
    Title PED Volume as Determined by SD OCT Analysis
    Description Change in ratio of volume of PED, calculated as change from baseline divided by baseline value.
    Time Frame Baseline to Week 52

    Outcome Measure Data

    Analysis Population Description
    Participants present for both baseline and week 52 assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Standard Deviation) [ratio]
    0.08
    (0.9)
    26. Other Pre-specified Outcome
    Title PED Height as Determined by SD OCT Analysis
    Description Ratio of change in height of PED, calculated as change from baseline divided by baseline value
    Time Frame Baseline, week 24

    Outcome Measure Data

    Analysis Population Description
    Participants present for both baseline and week 24 assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Inter-Quartile Range) [ratio]
    0.26
    27. Other Pre-specified Outcome
    Title PED Height as Determined by SD OCT Analysis
    Description Ratio of change in height of PED, calculated as change from baseline divided by baseline value
    Time Frame Baseline, week 52

    Outcome Measure Data

    Analysis Population Description
    Participants present for both baseline and week 52 assessment
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    Measure Participants 24
    Mean (Inter-Quartile Range) [ratio]
    0.38

    Adverse Events

    Time Frame 52 weeks
    Adverse Event Reporting Description
    Arm/Group Title IAI Treatment
    Arm/Group Description Intravitreal injection of aflibercept 2 mg/0.05 ml at baseline, week 4, week 8, week 16, week 24, week 36, and week 48. Aflibercept Ophthalmic: IAI given for active exudative macular degeneration (CNV, SRF, PED) per SOC optovue angiovue: FDA approved Optovue Angiovue will be used to monitor progression and responsiveness of active exudative macular degeneration to IAI.
    All Cause Mortality
    IAI Treatment
    Affected / at Risk (%) # Events
    Total 0/26 (0%)
    Serious Adverse Events
    IAI Treatment
    Affected / at Risk (%) # Events
    Total 1/26 (3.8%)
    Eye disorders
    Retinal detachment 1/26 (3.8%) 1
    Other (Not Including Serious) Adverse Events
    IAI Treatment
    Affected / at Risk (%) # Events
    Total 2/26 (7.7%)
    Infections and infestations
    Pneumonia 1/26 (3.8%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplastic syndrome 1/26 (3.8%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. David Sarraf
    Organization Stein Eye Institute of UCLA
    Phone 310-825-7836
    Email DSarraf@ucla.edu
    Responsible Party:
    David Sarraf, MD, Principal Investigator, University of California, Los Angeles
    ClinicalTrials.gov Identifier:
    NCT03022292
    Other Study ID Numbers:
    • 16-000925
    First Posted:
    Jan 16, 2017
    Last Update Posted:
    Jan 6, 2022
    Last Verified:
    Dec 1, 2021